Tumour growth stimulation following partial hepatectomy in mice is associated with increased upregulation of c-Met
- Nadia Harun,
- Patricia Costa,
- C. Christophi
- … show all 3 hide
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Hepatic resection is the preferred option for curative treatment of colorectal liver metastasis (CLM). However, this is associated with significant recurrence rates in both hepatic and extrahepatic sites. The upregulation of growth factors required for liver regeneration after resection is thought to stimulate the growth of micrometastases. The current study describes temporal changes in the expression of hepatocyte growth factor receptor (c-Met), epidermal growth factor receptor (EGFR) and insulin growth factor I receptor (IGF-IR) in an orthotopic mouse model of liver resection and tumour induction. Mice underwent 70 % hepatectomy and induction of liver metastases through intrasplenic injection of colorectal cancer cells. Control groups included sham-operated mice and 70 % hepatectomy alone. The expression levels of liver and tumour c-Met, EGFR and IGF-IR were quantified by quantitative RT-PCR at different time points. 70 % liver resection stimulates tumour growth; increases the expression of c-Met within established tumours and surrounding liver parenchyma; downregulates EGFR expression and increases IGF-IR expression within the liver parenchyma. In conclusion, we demonstrate in our mouse model that major hepatectomy stimulates engraftment and growth of CLM and that this effect is probably due to the upregulation of c-Met as a result of the liver regeneration process. Liver IGF-IR may also contribute to this phenomenon through a paracrine effect on tumour growth. This study provides support for the role of c-Met in the stimulation of tumour growth after resection possibly through the promotion of tumour cell proliferation.
- Saenz, NC, Cady, B, McDermott, WV, Steele, GD (1989) Experience with colorectal carcinoma metastatic to the liver. Surg Clin North Am 69: pp. 361-370
- Pestana, C, Reitemeier, RJ, Moertel, CG, Judd, ES, Dockerty, MB (1964) The natural history of carcinoma of the colon and rectum. Am J Surg 108: pp. 826-829 CrossRef
- Koh, SL, Ager, EI, Christophi, C (2010) Liver regeneration and tumour stimulation: implications of the renin-angiotensin system. Liver Int 30: pp. 1414-1426 CrossRef
- Christophi, C, Harun, N, Fifis, T (2008) Liver regeneration and tumor stimulation–a review of cytokine and angiogenic factors. J Gastrointest Surg 12: pp. 966-980 CrossRef
- Jong, MC, Pulitano, C, Ribero, D, Strub, J, Mentha, G, Schulick, RD, Choti, MA, Aldrighetti, L, Capussotti, L, Pawlik, TM (2009) Rates and patterns of recurrence following curative intent surgery for colorectal liver metastasis: an international multi-institutional analysis of 1669 patients. Ann Surg 250: pp. 440-448
- Lukomska, B, Dluzniewska, J, Polanski, J, Zajac, L (2004) Expression of growth factors in colorectal carcinoma liver metastatic patients after partial hepatectomy: implications for a functional role in cell proliferation during liver regeneration. Comp Hepatol 3: pp. S52 CrossRef
- Dluzniewska, J, Zolich, D, Polanski, J, Zajac, L, Sitkiewicz, D, Lukomska, B (2002) Hepatocyte growth factor levels in liver and blood, and post-operative liver cell proliferation in patients with benign and malignant liver tumors after partial hepatectomy. Med Sci Monit 8: pp. 690-696
- Yoon, SS, Kim, SH, Gonen, M, Heffernan, NM, Detwiller, KY, Jarnagin, WR, D’Angelica, M, Blumgart, LH, Tanabe, KK, Dematteo, RP (2006) Profile of plasma angiogenic factors before and after hepatectomy for colorectal cancer liver metastases. Ann Surg Oncol 13: pp. 353-362 CrossRef
- Rupertus, K, Kollmar, O, Scheuer, C, Junker, B, Menger, MD, Schilling, MK (2007) Major but not minor hepatectomy accelerates engraftment of extrahepatic tumor cells. Clin Exp Metastasis 24: pp. 39-48 CrossRef
- Huh, CG, Factor, VM, Sanchez, A, Uchida, K, Conner, EA, Thorgeirsson, SS (2004) Hepatocyte growth factor/c-met signaling pathway is required for efficient liver regeneration and repair. Proc Natl Acad Sci USA 101: pp. 4477-4482 CrossRef
- Michalopoulos, GK, Khan, Z (2005) Liver regeneration, growth factors, and amphiregulin. Gastroenterology 128: pp. 503-506 CrossRef
- Natarajan, A, Wagner, B, Sibilia, M (2007) The EGF receptor is required for efficient liver regeneration. Proc Natl Acad Sci USA 104: pp. 17081-17086 CrossRef
- Bohm, F, Kohler, UA, Speicher, T, Werner, S (2010) Regulation of liver regeneration by growth factors and cytokines. EMBO Mol Med 2: pp. 294-305 CrossRef
- Factor, VM, Seo, D, Ishikawa, T, Kaposi-Novak, P, Marquardt, JU, Andersen, JB, Conner, EA, Thorgeirsson, SS (2010) Loss of c-Met disrupts gene expression program required for G2/M progression during liver regeneration in mice. PLoS One 5: pp. e12739 CrossRef
- Desbois-Mouthon, C, Wendum, D, Cadoret, A, Rey, C, Leneuve, P, Blaise, A, Housset, C, Tronche, F, Bouc, Y, Holzenberger, M (2006) Hepatocyte proliferation during liver regeneration is impaired in mice with liver-specific IGF-1R knockout. FASEB J 20: pp. 773-775
- Peruzzi, B, Bottaro, DP (2006) Targeting the c-Met signaling pathway in cancer. Clin Cancer Res 12: pp. 3657-3660 CrossRef
- Maulik, G, Shrikhande, A, Kijima, T, Ma, PC, Morrison, PT, Salgia, R (2002) Role of the hepatocyte growth factor receptor, c-Met, in oncogenesis and potential for therapeutic inhibition. Cytokine Growth Factor Rev 13: pp. 41-59 CrossRef
- Normanno, N, Luca, A, Bianco, C, Strizzi, L, Mancino, M, Maiello, MR, Carotenuto, A, Feo, G, Caponigro, F, Salomon, DS (2006) Epidermal growth factor receptor (EGFR) signaling in cancer. Gene 366: pp. 2-16 CrossRef
- Dvorak, HF, Detmar, M, Claffey, KP, Nagy, JA, Water, L, Senger, DR (1995) Vascular permeability factor/vascular endothelial growth factor: an important mediator of angiogenesis in malignancy and inflammation. Int Arch Allergy Immunol 107: pp. 233-235 CrossRef
- Hellstrom, I, Hellstrom, KE, Nishioka, M (1975) Reactivity to tumour-associated antigens detected in mice undergoing liver regeneration. Nat 253: pp. 744-746 CrossRef
- Picardo, A, Karpoff, HM, Ng, B, Lee, J, Brennan, MF, Fong, Y (1998) Partial hepatectomy accelerates local tumor growth: potential roles of local cytokine activation. Surg 124: pp. 57-64 CrossRef
- Asaga, T, Suzuki, K, Umeda, M, Sugimasa, Y, Takemiya, S, Okamoto, T (1991) The enhancement of tumor growth after partial hepatectomy and the effect of sera obtained from hepatectomized rats on tumor cell growth. Jpn J Surg 21: pp. 669-675 CrossRef
- Krause, P, Flikweert, H, Monin, M, Seif Amir Hosseini, A, Helms, G, Cantanhede, G, Ghadimi, BM, Koenig, S (2013) Increased growth of colorectal liver metastasis following partial hepatectomy. Clin Exp Metastasis 30: pp. 681-693 CrossRef
- Harun, N, Nikfarjam, M, Muralidharan, V, Christophi, C (2007) Liver regeneration stimulates tumor metastases. J Surg Res 138: pp. 284-290 CrossRef
- Neo, JH, Malcontenti-Wilson, C, Muralidharan, V, Christophi, C (2007) Effect of ACE inhibitors and angiotensin II receptor antagonists in a mouse model of colorectal cancer liver metastases. J Gastroenterol Hepatol 22: pp. 577-584 CrossRef
- Kuruppu, D, Christophi, C, Bertram, JF, O’Brien, PE (1996) Characterization of an animal model of hepatic metastasis. J Gastroenterol Hepatol 11: pp. 26-32 CrossRef
- Nagel, JD, Kort, WJ (1992) A new liver-tumor model in the rat. Cancer Chemother Pharmacol 30: pp. 70-72 CrossRef
- Nikfarjam, M, Malcontenti-Wilson, C, Fanartzis, M, Daruwalla, J, Christophi, C (2004) A model of partial hepatectomy in mice. J Invest Surg 17: pp. 291-294 CrossRef
- Ager, EI, Chong, WW, Wen, SW, Christophi, C (2010) Targeting the angiotensin II type 2 receptor (AT2R) in colorectal liver metastases. Cancer Cell Int 10: pp. 19 CrossRef
- Stolz, DB, Mars, WM, Petersen, BE, Kim, TH, Michalopoulos, GK (1999) Growth factor signal transduction immediately after two-thirds partial hepatectomy in the rat. Cancer Res 59: pp. 3954-3960
- Meredith, K, Haemmerich, D, Qi, C, Mahvi, D (2007) Hepatic resection but not radiofrequency ablation results in tumor growth and increased growth factor expression. Ann Surg 245: pp. 771-776 CrossRef
- Lim, C, Cauchy, F, Azoulay, D, Farges, O, Ronot, M, Pocard, M (2013) Tumour progression and liver regeneration-insights from animal models. Nat Rev Gastroenterol Hepatol.
- Tanaka, K, Hiroshima, Y, Nakagawa, K, Kumamoto, T, Nojiri, K, Takeda, K, Ota, M, Ichikawa, Y, Endo, I (2013) Two-stage hepatectomy with effective perioperative chemotherapy does not induce tumor growth or growth factor expression in liver metastases from colorectal cancer. Surg 153: pp. 179-188 CrossRef
- Stolz, DB, Ross, MA, Salem, HM, Mars, WM, Michalopoulos, GK, Enomoto, K (1999) Cationic colloidal silica membrane perturbation as a means of examining changes at the sinusoidal surface during liver regeneration. Am J Pathol 155: pp. 1487-1498 CrossRef
- Michalopoulos, GK, DeFrances, MC (1997) Liver regeneration. Sci 276: pp. 60-66 CrossRef
- Ross, MA, Sander, CM, Kleeb, TB, Watkins, SC, Stolz, DB (2001) Spatiotemporal expression of angiogenesis growth factor receptors during the revascularization of regenerating rat liver. Hepatol 34: pp. 1135-1148 CrossRef
- Borowiak, M, Garratt, AN, Wustefeld, T, Strehle, M, Trautwein, C, Birchmeier, C (2004) Met provides essential signals for liver regeneration. Proc Natl Acad Sci U S A 101: pp. 10608-10613 CrossRef
- Santos, A, Yusta, B, Fernandez-Moreno, MD, Blazquez, E (1994) Expression of insulin-like growth factor-I (IGF-I) receptor gene in rat brain and liver during development and in regenerating adult rat liver. Mol Cell Endocrinol 101: pp. 85-93 CrossRef
- Michalopoulos, GK (2010) Liver regeneration after partial hepatectomy: critical analysis of mechanistic dilemmas. Am J Pathol 176: pp. 2-13 CrossRef
- Warren, RS, Yuan, H, Matli, MR, Gillett, NA, Ferrara, N (1995) Regulation by vascular endothelial growth factor of human colon cancer tumorigenesis in a mouse model of experimental liver metastasis. J Clin Invest 95: pp. 1789-1797 CrossRef
- Baker, CH, Kedar, D, McCarty, MF, Tsan, R, Weber, KL, Bucana, CD, Fidler, IJ (2002) Blockade of epidermal growth factor receptor signaling on tumor cells and tumor-associated endothelial cells for therapy of human carcinomas. Am J Pathol 161: pp. 929-938 CrossRef
- Wu, Y, Yakar, S, Zhao, L, Hennighausen, L, LeRoith, D (2002) Circulating insulin-like growth factor-I levels regulate colon cancer growth and metastasis. Cancer Res 62: pp. 1030-1035
- Winder, T, Lenz, HJ (2010) Vascular endothelial growth factor and epidermal growth factor signaling pathways as therapeutic targets for colorectal cancer. Gastroenterol 138: pp. 2163-2176 CrossRef
- Bid, HK, Zhan, J, Phelps, DA, Kurmasheva, RT, Houghton, PJ (2012) Potent inhibition of angiogenesis by the IGF-1 receptor-targeting antibody SCH717454 is reversed by IGF-2. Mol Cancer Ther 11: pp. 649-659 CrossRef
- Renzo, MF, Olivero, M, Giacomini, A, Porte, H, Chastre, E, Mirossay, L, Nordlinger, B, Bretti, S, Bottardi, S, Giordano, S (1995) Overexpression and amplification of the met/HGF receptor gene during the progression of colorectal cancer. Clin Cancer Res 1: pp. 147-154
- Oliveira, AT, Matos, D, Logullo, AF, DAS, SR, Neto, RA, Filho, AL, Saad, SS (2009) MET Is highly expressed in advanced stages of colorectal cancer and indicates worse prognosis and mortality. Anticancer Res 29: pp. 4807-4811
- Sierra, JR, Tsao, MS (2011) c-MET as a potential therapeutic target and biomarker in cancer. Ther Adv Med Oncol 3: pp. S21-S35 CrossRef
- Efferth, T (2012) Signal transduction pathways of the epidermal growth factor receptor in colorectal cancer and their inhibition by small molecules. Curr Med Chem 19: pp. 5735-5744 CrossRef
- Ewing, GP, Goff, LW (2010) The insulin-like growth factor signaling pathway as a target for treatment of colorectal carcinoma. Clin Colorectal Cancer 9: pp. 219-223 CrossRef
- Horiguchi, N, Takayama, H, Toyoda, M, Otsuka, T, Fukusato, T, Merlino, G, Takagi, H, Mori, M (2002) Hepatocyte growth factor promotes hepatocarcinogenesis through c-Met autocrine activation and enhanced angiogenesis in transgenic mice treated with diethylnitrosamine. Oncog 21: pp. 1791-1799 CrossRef
- Casanova, ML, Larcher, F, Casanova, B, Murillas, R, Fernandez-Acenero, MJ, Villanueva, C, Martinez-Palacio, J, Ullrich, A, Conti, CJ, Jorcano, JL (2002) A critical role for ras-mediated, epidermal growth factor receptor-dependent angiogenesis in mouse skin carcinogenesis. Cancer Res 62: pp. 3402-3407
- Xue, M, Cao, X, Zhong, Y, Kuang, D, Liu, X, Zhao, Z, Li, H (2012) Insulin-like growth factor-1 receptor (IGF-1R) kinase inhibitors in cancer therapy: advances and perspectives. Curr Pharm Des 18: pp. 2901-2913 CrossRef
- Pietras, K, Pahler, J, Bergers, G, Hanahan, D (2008) Functions of paracrine PDGF signaling in the proangiogenic tumor stroma revealed by pharmacological targeting. PLoS Med 5: pp. e19 CrossRef
- Fifis, T, Malcontenti-Wilson, C, Amijoyo, J, Anggono, B, Muralidharan, V, Nikfarjam, M, Christophi, C (2011) Changes in growth factor levels after thermal ablation in a murine model of colorectal liver metastases. HPB 13: pp. 246-255 CrossRef
- Wu, F, Wu, L, Zheng, S, Ding, W, Teng, L, Wang, Z, Ma, Z, Zhao, W (2006) The clinical value of hepatocyte growth factor and its receptor–c-met for liver cancer patients with hepatectomy. Dig Liver Dis 38: pp. 490-497 CrossRef
- Osada, S, Matsui, S, Komori, S, Yamada, J, Sanada, Y, Ihawa, A, Tanaka, Y, Tokuyama, Y, Okumura, N, Nonaka, K, Hosono, Y, Takahashi, T, Yamaguchi, K, Yoshida, K (2010) Effect of hepatocyte growth factor on progression of liver metastasis in colorectal cancer. Hepatogastroenterol 57: pp. 76-80
- Greenall, SA, Gherardi, E, Liu, Z, Donoghue, JF, Vitali, AA, Li, Q, Murphy, R, Iamele, L, Scott, AM, Johns, TG (2012) Non-agonistic bivalent antibodies that promote c-MET degradation and inhibit tumor growth and others specific for tumor related c-MET. PLoS ONE 7: pp. e34658 CrossRef
- Jong, GM, Hendriks, T, Eek, A, Oyen, WJ, Nagtegaal, ID, Bleichrodt, RP, Boerman, OC (2011) Adjuvant radioimmunotherapy improves survival of rats after resection of colorectal liver metastases. Ann Surg 253: pp. 336-341 CrossRef
- Wu, Y, Brodt, P, Sun, H, Mejia, W, Novosyadlyy, R, Nunez, N, Chen, X, Mendoza, A, Hong, SH, Khanna, C, Yakar, S (2010) Insulin-like growth factor-I regulates the liver microenvironment in obese mice and promotes liver metastasis. Cancer Res 70: pp. 57-67 CrossRef
- Karpoff, HM, Tung, C, Ng, B, Fong, Y (1996) Interferon gamma protects against hepatic tumor growth in rats by increasing Kupffer cell tumoricidal activity. Hepatol 24: pp. 374-379 CrossRef
- Ono, M, Tanaka, N, Orita, K (1986) Complete regression of mouse hepatoma transplanted after partial hepatectomy and the immunological mechanism of such regression. Cancer Res 46: pp. 5049-5053
- Title
- Tumour growth stimulation following partial hepatectomy in mice is associated with increased upregulation of c-Met
- Journal
-
Clinical & Experimental Metastasis
Volume 31, Issue 1 , pp 1-14
- Cover Date
- 2014-01-01
- DOI
- 10.1007/s10585-013-9604-7
- Print ISSN
- 0262-0898
- Online ISSN
- 1573-7276
- Publisher
- Springer Netherlands
- Additional Links
- Topics
- Keywords
-
- Hepatectomy
- Liver regeneration
- Liver metastases
- Growth factors
- c-Met
- Industry Sectors
- Authors
-
- Nadia Harun (1)
- Patricia Costa (1)
- C. Christophi (1)
- Author Affiliations
-
- 1. Department of Surgery, AH/NH Austin Hospital, University of Melbourne, Heidelberg, VIC, 3084, Australia